We will study several aspects of B cell differentiation in mice and humans. We will determine the lifetime of messenger RNA for Mu chains in resting B cells. We will investigate the mechanism of suppression of B cell differentiation by anti-Mu antibodies by determining whether the block in IgM secretion occurs at the level of transcription of Mu mRNA, processing of mRNA to yield the Mu secreted message, or translation. We will determine whether isotype switching occurs in anti-Mu suppressed cells by probing for deletion of CMu genes. To further examine the mechanisms of isotype switching we will study the effects of suppression of IgG3 synthesis, in vivo and in vitro, on expression of 3 feet encoded isotypes. We will attempt to derive a transformed cell line from human neonatal blood which simultaneously expresses sIgM and sIgA. We will continue studies of human B cell differentiation, focussing on synergistic interactions of different polyclonal activators which may address distict functional subpopulations of B cells. The long term goals of this research are to develop methods which may be applied to study of the permanent defects in B cell differentiation responsible for the common forms of hypogammaglobulinemia, and the transient defects which interfere with effective immunization of the newborn against common bacterial pathogens.